PT  - JOURNAL ARTICLE
AU  - Stephen Jordan
AU  - Erroll Spridgen
AU  - Virgina Fisher
AU  - Jennifer Hincks
AU  - Tony Grasiewicz
AU  - Ken Meecham
TI  - Acute markers of neutrophilic lung infiltration in the non-human primate LPS model
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - P1788
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/P1788.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/P1788.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - The non-human primate LPS model bridges the translation between pre-clinical rodent and LPS proof of concept studies in healthy volunteers. The response to LPS in the primate is documented at 24h and beyond but less data is available at earlier time points generally utilised in endotoxin exposure studies in man.The aim of this study was to determine whether the temporal inflammatory response at 6 and 24h following LPS exposure in the cynomologus monkey was similar to man and that observed in rodent studies. The study also evaluated the efficacy of an oral glucocorticoid against measures of pulmonary inflammation.Four primates in a cross over design, underwent a recovery segmental bronchoalveolar Lavage (BAL) pre-treatment, 6 and 24h following aerosolised LPS exposure. Two animals were administered vehicle and two dexamethasone by oral gavage 1h prior and 7h post LPS exposure. Exposure to LPS produced a significant (p<0.05) recruitment of BAL neutrophils at 6h (5-6 fold increase v pre-treatment) and peaked at 24h (8-10 fold increase v pre-treatment). An increase in BAL macrophages (1.8 fold compared to pre-treatment) was recorded at the 24h time point. The pro-inflammatory cytokine response (IL-6;816 pg/mL, IL-8;1112 pg/mL, MIP-1α;77 pg/mL, MCP-1;2618 pg/mL and TNF-α;543 pg/ml peaked at 6h and remained significantly higher than pre-treatment out to 24h post exposure. Oral administration of dexamethasone (3 mg/kg b.i.d) attenuated the inflammatory response at both time points.The rapid increase in soluble markers and neutrophilic lung infiltration measured in healthy volunteers and rodents is replicated in early time points following LPS exposure in the steroid sensitive non-human primate model.